Point-of-Care Nucleic Acid Test for Cytomegalovirus for Newborn Hearing Screening

描述(由申请人提供)：在美国，普遍的新生儿听力筛查是强制性的，并在产后医院进行。目前基于生理的听力筛查测试无法检测到由巨细胞病毒(CMV)感染引起的迟发性听力损失。因此，提出了一种补充筛查方法，通过早期发现和干预来预防与CMV相关的听力损失相关的残疾。一种核酸测试已经被描述为使用唾液样本来筛查新生儿先天性CMV感染，在这种样本中，它比新生儿筛查实验室传统使用的干血斑点更敏感。新生儿筛查项目没有使用新生儿唾液样本和分子分析所需的基础设施。Advanced Liquid Logic的数字微流控技术是公认的创新、低成本和自动化的液体处理系统，可以应对这一挑战。这个Fast-Track应用程序的目标是开发一种集成的芯片实验室，使用唾液样本对新生儿先天性CMV感染进行筛查。第一阶段的具体目标是开发从唾液样本中提纯CMV和在盒上进行病毒DNA扩增的方案，并在数字微流控平台上集成一种“样本到答案”的CMV筛查方法。第一阶段的成功将导致第二阶段的延续，具体目标将是(I)开发一个新生儿护理点筛查平台，(Ii)在该平台上优化“样本到答案”CMV方案并评估其分析性能，以及(Iii)与阿拉巴马大学伯明翰分校合作，使用新生儿唾液样本进行与“黄金标准”快速唾液培养的方法比较。

DESCRIPTION (provided by applicant): Universal newborn hearing screening is mandated in the US and is performed in the postpartum hospital setting. Current physiology-based hearing screening tests are unable to detect late-onset hearing loss caused by cytomegalovirus (CMV) infection. Therefore, a complementary screening approach has been suggested to prevent disabilities associated with CMV-related hearing loss by early detection and intervention. A nucleic acid test has been described to screen newborns for congenital CMV infection using saliva specimens where it is more sensitive than the dried blood spots traditionally used by the newborn screening laboratories. Newborn screening programs do not have the infrastructure necessary to use newborn saliva samples and molecular assays. Advanced Liquid Logic's digital microfluidic technology is a recognized innovative, low-cost, and automated liquid handling system that can address this challenge. The objective of this Fast-Track application is to develop an integrated lab-on-a-chip to perform screening of congenital CMV infection in newborns using saliva samples. Specific aims in Phase I are to develop protocols for CMV purification from saliva samples and for viral DNA amplification on-cartridge, and to integrate a "sample-to-answer" CMV screening assay on the digital microfluidic platform. Success in Phase I will result in a Phase II continuation where the specific aims will be (i) to develop a point-of-care newborn screening platform, (ii) to optimize the "sample-to-answer" CMV protocol in this platform and assess its analytical performance, and (iii) to perform a method comparison with the "gold standard" rapid saliva culture using neonatal saliva samples in collaboration with the University of Alabama at Birmingham.